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PubMed2000

Clarithromycin suppresses bronchial hyperresponsiveness associated with eosinophilic inflammation in patients with asthma.

BACKGROUND: Although long-term administration of 14-membered macrolide antibiotics is a therapeutic alternative in asthma, both its pharmacologic mechanism of action and association with the pathogenesis of asthma remain obscure. OBJECTIVE: This study investigated the suppressive effect of clarithromycin on airway responsiveness to methacholine provocation testing and examined whether chrarithromycin's antiasthmatic activity is associated with a reduction in eosinophilic inflammation. METHODS: For 8 weeks, patients received 200 mg of clarithromycin or identical-appearing placebo twice daily. We assessed the effects of treatment with clarithromycin on bronchoconstriction precipitated by inhalation of methacholine in 17 adults with mild or moderate bronchial asthma who were in stable clinical condition. A double-blind, randomized, crossover design was used. Eosinophil counts and eosinophilic cationic protein (ECP) levels were determined in blood and sputum samples obtained on the morning of the methacholine provocation testing day. RESULTS: After 8 weeks of treatment with clarithromycin, patients' symptoms, blood and sputum eosinophils counts and sputum ECP levels were significantly decreased compared with both placebo and baseline. Furthermore, values of PC20 methacholine improved in all patients after clarithromycin treatment. CONCLUSIONS: Clarithromycin has a bronchial anti-inflammatory effect associated with decreased eosinophilic infiltration. This study suggests interesting therapeutic possibilities for bronchial asthma that warrant further trials.

Adult↗
PubMed2000

Effect of pretreatment antibiotic resistance to metronidazole and clarithromycin on outcome of Helicobacter pylori therapy: a meta-analytical approach.

Our purpose was to define the effect of pretreatment Helicobacter pylori resistance to metronidazole or to clarithromycin on the success of antimicrobial therapy. We used 75 key words to perform a literature search in MEDLINE as well as manual searches to identify clinical treatment trials that provided results in relation to H. pylori susceptibility to metronidazole and clarithromycin or both during the period 1984-1997 (abstracts were not included). Meta-analysis was done with both fixed- and random-effect models; results were shown using Galbraith's radial plots. We identified 49 papers with 65 arms for metronidazole (3594 patients, 2434 harboring H. pylori strains sensitive to metronidazole and 1160 harboring resistant strains). Metronidazole resistance reduced effectiveness by an average of 37.7% (95% CI = 29.6-45.7%). The variability in the risk difference for metronidazole was 122.0 to -90.6 and the chi-square value for heterogeneity was significant (P<0.001). Susceptibility tests for clarithromycin were performed in 12 studies (501 patients, 468 harboring H. pylori strains sensitive to clarithromycin and 33 harboring resistant strains). Clarithromycin resistance reduced effectiveness by an average of 55% (95% CI = 33-78%). We found no common factors that allowed patients to be divided into subgroups with additional factors significantly associated with resistance. In conclusion, metronidazole or clarithromycin pretreatment resistant H. pylori are the main factors responsible for treatment failure with regimens using these compounds. If H. pylori antibiotic resistance continues to increase, pretherapy antibiotic sensitivity testing might become necessary in many regions.

Anti-Bacterial Agents↗
PubMed2001

Effect of clarithromycin and itraconazole on the pharmacokinetics of ropivacaine.

In a double-blind, randomised, three-way cross-over study, eight healthy volunteers ingested daily for 4 days either 250 mg clarithromycin twice daily, 200 mg itraconazole once daily, or placebo. On day 4, each subject received a single dose of 0.6 mg kg-1 ropivacaine intravenously over 30 min. Ropivacaine and (S)-2',6'-pipecoloxylidide in venous plasma and urine samples were measured for up to 12 hours and 24 hours, respectively. There were no significant changes in the pharmacokinetic parameters of the parent ropivacaine after ingestion of clarithromycin or itraconazole. However, the peak plasma concentration and AUC of (S)-2',6'-pipecoloxylidide metabolite were significantly decreased in both the clarithromycin and itraconazole phases, compared with the placebo phase. The fraction of ropivacaine metabolised to (S)-2',6'-pipecoloxylidide excreted in urine was decreased in the itraconazole phase. Both clarithromycin and itraconazole inhibit the CYP3A4 mediated formation of (S)-2',6'-pipecoloxylidide from ropivacaine. With the doses used, itraconazole is a stronger inhibitor than clarithromycin. The interaction of clarithromycin with ropivacaine seems to be dose (concentration)-dependent.

Administration, Oral↗
PubMed1998

Influence of clarithromycin dosage on pantoprazole combined triple therapy for eradication of Helicobacter pylori.

BACKGROUND: Low-dose clarithromycin (250 mg b.d.) in combination with omeprazole and metronidazole has been recommended for the eradication of Helicobacter pylori. Whether the substitution of omeprazole by pantoprazole requires adjustment of the clarithromycin dose is not known. AIM: To directly compare the efficacy and tolerability of two different dosages of clarithromycin in combination with pantoprazole and metronidazole. METHODS: One hundred and sixty-three patients with endoscopically confirmed gastritis, gastric or duodenal ulcers and positive H. pylori findings in the rapid urease test were randomized and treated for 7 days with pantoprazole (40 mg b.d.). metronidazole (500 mg b.d.) and clarithromycin using either a regimen of 500 mg b.d. (group PMC 500) or 250 mg b.d. (group PMC 250). Eradication success was determined no less than 4 weeks after concluding therapy using the 13C-urea breath test. RESULTS: One-hundred and thirty-nine patients completed the study. Based on a per protocol analysis. successful eradication was documented in 63/70 patients (90.0%) in group PMC 500 and in 62/69 patients (89.9%) in group PMC 250. Based on the intention-to-treat analysis, eradication rates were 78.8% (group PMC 500) and 75.6% (group PMC 250). The incidence of adverse effects was significantly higher in patients receiving PMC 500 (50.0%) than in those receiving PMC 250 (25.4%). CONCLUSIONS: Triple therapy with pantoprazole, metronidazole and clarithromycin provides an efficient eradication regimen for H. pylori infection. A low dose of clarithromycin is equal to a higher dose in therapeutic efficacy and it offers the advantage of improved tolerance and lower cost.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori--a randomized, controlled trial.

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.

Adult↗
PubMed2000

Effect of ornidazole and clarithromycin resistance on eradication of Helicobacter pylori in peptic ulcer disease.

BACKGROUND: Clarithromycin and nitroimidazoles such as metronidazole and ornidazole are among the most frequently used antibiotics for curing Helicobacter pylori infection. However, controversial data exist on whether their in vitro resistance has a negative impact on treatment outcome. METHODS: Patients with H. pylori positive active peptic ulcer disease were randomly assigned to receive lansoprazole 30 mg o.d., amoxycillin 1 g b.d. and ornidazole 500 mg b.d. (LAO) or lansoprazole 30 mg o.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC) for 2 weeks. Pre-treatment resistance to ornidazole and clarithromycin was assessed by Epsilometer (E-) test. Four weeks after completion of treatment, patients underwent a 13C urea breath test to assess H. pylori status. RESULTS: Data from 80 patients with active peptic ulcer disease and positive H. pylori status were analysed. The prevalence of primary drug resistance was 25% for metronidazole and 7.5% for clarithromycin. In patients treated with LAO, effective treatment was achieved in 87% of metronidazole-susceptible, but only 30% of metronidazole-resistant strains (P < 0.01). In the LAC group, therapy was successful in 81% of clarithromycin-susceptible strains, whereas treatment failed in all patients with primary clarithromycin resistance (n = 3). CONCLUSION: Resistance against nitroimidazoles significantly affects treatment outcome in H. pylori eradication therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Open label trial of oral clarithromycin in active Crohn's disease.

BACKGROUND: Crohn's disease seems likely to be due in some way to bacteria. Clarithromycin is a broad spectrum macrolide antibiotic with good penetration into macrophages and may be effective in eradicating the organisms that are presumed to be at the centre of the granulomatous reaction in Crohn's disease. METHODS: Twenty-five patients with active Crohn's disease were treated with oral clarithromycin 250 mg b.d. in an open label study. Treatment was for an initial 4-week period, continued to 12 weeks in patients who had shown a partial or complete response. The patients had a median age of 30 years (range 17-72), and disease duration of 5 years (range 2 months-28 years); 14 had ileocolonic, four small bowel, seven colonic disease and 10 had previous resections. Twenty patients were receiving a 5-ASA preparation, 15 corticosteroids (prednisolone median dose 10 mg range 2-30 mg) and nine azathioprine. All patients receiving corticosteroids or azathioprine had been on unchanged treatment for at least 12 weeks. RESULTS: Median pre-treatment Harvey Bradshaw index (HBI) was 9 (range 5-16) and median serum C-reactive protein was 21.5 mg/L (range < 5-117). By 4 weeks the median HBI had decreased to 5 (range 0-18) (P < 0.001) and median CRP to 17 mg/L (range < 5-157) (P=0.16). Sixteen patients (64%) had at least a 3 point fall in HBI and remission (defined as a HBI less than or equal to 4) was achieved in 12 patients (48%). By 12 weeks median HBI was 5 (range 0-18) (P < 0.001) and median CRP was 14.5 mg/L (range < 5-157) (P=0.05). Eleven of the 25 patients studied continued on oral clarithromycin after 12 weeks for a median of 28 weeks (range 20-60). Eight (73%) remained in remission on treatment. When treatment with clarithromycin was stopped three remained in remission and five relapsed after a median of 5 months (range 4-9). Two patients withdrew due to non-serious side-effects. Treatment was well tolerated in the remaining patients. CONCLUSION: This open label study has shown an impressive response to clarithromycin in a group of patients with active Crohn's disease, many of whom had been resistant to other therapy. A formal randomized controlled trial of clarithromycin in active Crohn's disease is needed.

Adolescent↗
PubMed2000

Rabeprazole, amoxycillin and low- or high-dose clarithromycin for cure of Helicobacter pylori infection.

BACKGROUND: Rabeprazole sodium is a proton pump inhibitor. AIM: To evaluate the efficacy and safety of 1-week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori. METHODS: A total of 100 subjects with H. pylori were randomly divided into two groups of 1-week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b. d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E-test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment. RESULTS: There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention-to-treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76-95%) and 89% (95% CI: 80-97%); RAC800: 94% (95% CI: 87-100%) and 97% (95% CI: 94-100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin-resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group. CONCLUSION: One-week triple therapy with rabeprazole, amoxycillin and low-dose clarithromycin is effective for the eradication of H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Clarithromycin reduces Isus and Ito currents in human atrial myocytes with minor repercussions on action potential duration.

The macrolide antibacterial agent clarithromycin has been shown to cause QT interval prolongation on the electrocardiogram. In rabbit heart preparations clarithromycin (concentration dependently) lengthened the action potential duration and blocked the delayed rectifier current. The aim of the present study was to investigate the clarithromycin effects: (i) on the Ca2+ L-type and the main K+ repolarizing currents on human atrial myocytes, using whole-cell patch clamp recordings and (ii) on action potentials recorded from human atrial and ventricular myocardium using conventional microelectrodes. It has been found that (i) 10-30 microM clarithromycin reduced the sustained current Isus significantly and that a 100 microM concentration was needed to cause a significant reduction in the transient outward current Ito, whereas clarithomycin did not affect the calcium current and (ii) clarithromycin (10-100 microM) prolonged the action potential duration in atrial preparations but did not alter the different parameters of the ventricular action potential. It is concluded that clarithromycin exerts direct cardiac electrophysiological effects that may contribute to pro-arrythmic potential.

Action Potentials↗
PubMed2001

Emergence of resistance to clarithromycin during treatment of disseminated cutaneous Mycobacterium chelonae infection: case report and literature review.

Results of in vitro susceptibility studies and one clinical trial have led to recommendations of clarithromycin monotherapy for the treatment of disseminated cutaneous Mycobacterium chelonae infections. We describe the case of a 65-year-old woman, immunocompromised by the use of chronic steroid therapy, who developed disseminated cutaneous infection with M. chelonae and failed clarithromycin monotherapy due to the development of drug resistance. In the relapse isolate we document the presence of a single point mutation at position 2058 in the gene coding for 23S rRNA peptidyltransferase regions, a mutation previously implicated in the development of resistance to clarithromycin. Two susceptible control isolates lacked the mutation. Three additional reports in the literature of patients developing recurrent skin lesions with clarithromycin-resistant M. chelonae following initial response to monotherapy are summarized. We demonstrate that clarithromycin monotherapy in patients with disseminated cutaneous infections can lead to clarithromycin resistance and therapeutic failure associated with a single point mutation at position 2058 of 23S rRNA.

Aged↗
PubMed2002

Increasing resistance of Helicobacter pylori to clarithromycin: is the horse bolting?

AIMS: To determine whether there has been a change in the patterns of susceptibility to various antibiotics of our isolates of Helicobacter pylori over a 5-year period from 1996 to 2000. METHODS: Five hundred and fourteen isolates of H. pylori grown from gastric biopsies were tested for susceptibility to amoxycillin, clarithromycin, metronidazole and tetracycline. The usage of macrolide antibiotics in Australia was examined by calculating the numbers of prescriptions issued under the Australian pharmaceutical benefits scheme between 1992 and 2000. RESULTS: There were no changes in susceptibility of H. pylori to amoxycillin and tetracycline and there was a slight decline in resistance to metronidazole. In contrast, there was a stepwise 4-fold increase from 3.8 to 15.7% in the number of isolates resistant to clarithromycin and a similar increase in the mean minimum inhibitory concentration of clarithromycin during the 5-year period of observation. There was no change in overall macrolide consumption in Australia over this and the preceding 3 years. However, the pattern changed, with erythromycin usage being halved and being replaced by roxithromycin and clarithromycin. CONCLUSIONS: Resistance of H. pylori to clarithromycin is increasing, possibly as a consequence of increased usage of roxithromycin and clarithromycin. More patients are likely to fail to respond to empirical therapy and will need microbiological investigation.

Amoxicillin↗
PubMed2001

Transfer of clarithromycin to gastric juice is enhanced by omeprazole in Helicobacter pylori-infected individuals.

BACKGROUND: The effects of proton-pump inhibitors and Helicobacter pylori infection on the distribution of drugs employed for the eradication of H. pylori are poorly understood. The aim of this study was to investigate the effects of a 7-day oral administration of 20 mg omeprazole on the distribution of clarithromycin in the gastric juice of individuals with H. pylori infection. METHODS: Eighteen H. pylori-infected dyspeptic male volunteers without endoscopic lesions were enrolled in a study with an open, randomized, two-period crossover design and a 21-day washout period between phases. Plasma and gastric juice concentrations of clarithromycin in subjects with and without omeprazole pretreatment were measured by means of liquid chromatography coupled to tandem mass spectrometry. RESULTS: The maximum concentration of clarithromycin (Cmax) and the area under the time-concentration curve from 0 to 2 h (AUC0-2h) were significantly higher in gastric juice than in plasma. Omeprazole treatment further augmented clarithromycin Cmax and AUC0-2h in gastric juice approximately 2-fold (P < 0.05). CONCLUSIONS: Short-term treatment with omeprazole in H. pylori-positive volunteers increases the amount of clarithromycin transferred to the gastric juice, confirming a synergism between these drugs. Our results suggest the presence of an active transport mechanism for clarithromycin from plasma to the gastric lumen, which is influenced by omeprazole.

Adult↗
PubMed2003

Necessity of multiple gastric biopsies from different sites for detection of clarithromycin-resistant Helicobacter pylori strains.

BACKGROUND: It has been reported that approximately 10% of patients infected with Helicobacter pylori have both clarithromycin-susceptible and clathromycin-resistant strains. However, there have been no reports indicating whether only one gastric biopsy is sufficient to detect clarithromycin-resistant strains. METHODS: Sixty-five H. pylori-infected patients were selected for this study, and 40 of them were given clarithromycin-based eradication therapy. Four gastric biopsies, 2 from the antrum and 2 from the corpus, were obtained from each of the 65 patients. Susceptibility of H. pylori strains to clarithromycin was examined by detecting mutations of the 23S ribosomal RNA (rRNA) gene of H. pylori. RESULTS: The clarithromycin-resistant strains were detected in 16 of the 65 (25%) patients. Only 5 of the 16 (31%) patients had the resistant strains in both the antrum and corpus. When only 1 or the other biopsy from the antrum was used, the resistant strains were detected in 8 (50%) or 9 (56%) of the 16 patients. CONCLUSIONS: These data indicate that multiple gastric biopsies from both the antrum and the corpus should be used to detect clarithromycin-resistant H. pylori strains.

Adult↗
PubMed1993

A single-blind, randomised, comparative study of clarithromycin and amoxycillin suspensions in the treatment of children with lower respiratory tract infections.

One hundred and forty-five children with signs and symptoms of lower respiratory tract infections were entered into this multicentre, General Practice, investigator-blind study, designed to demonstrate equivalent efficacy between clarithromycin and amoxycillin suspensions. Seventy one children were randomised to treatment with clarithromycin suspension 7.5 mg/kg bodyweight twice daily and 74 to treatment with amoxycillin suspension 125 mg (bodyweight < 25 kg) or 250 mg (bodyweight > or = 25 kg) three times a day according to bodyweight. Duration of therapy was 5-10 days as determined by the investigator. Clinical evaluations were performed pretreatment, during treatment and post-treatment within 72 hours of cessation of therapy. Fifty two children in the clarithromycin group and 57 in the amoxycillin group were clinically evaluable. Both study medications were effective and there were no significant differences between the groups with respect to clinical cure rate (60% for clarithromycin and 63% for amoxycillin), clinical success rate (cure plus improvement, 96% for clarithromycin and 95% for amoxycillin) or rate of resolution of clinical signs and symptoms in clinically evaluable patients. The intention to treat analysis for all patients entered similarly showed no significant differences in efficacy. The two treatment groups did not differ significantly with respect to incidence or severity of adverse events which were generally mild and associated with the gastrointestinal system. Therapy was withdrawn because of adverse events in three children on clarithromycin and one on amoxycillin. Bacteriological cure rates could not be determined because of an insufficient number of evaluable pre-treatment sputum samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗
PubMed1997

A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group.

Patients with AIDS and Mycobacterium avium complex (MAC) bacteremia are at high risk for relapse and emergence of resistant isolates during monotherapy with clarithromycin. Ninety-five AIDS patients with MAC bacteremia received clarithromycin plus clofazimine, with or without ethambutol, in a prospective, multicenter, randomized open-label trial. Of 80 patients with positive baseline cultures, sterilization or a 2 log10 reduction in colony-forming units of MAC in two consecutive blood cultures occurred in 69% of both groups. There were nine relapses in the two-drug arm and three in the three-drug arm. Kaplan-Meier estimates of risk of relapse at 36 weeks were 68% and 12%, respectively (P = .004). All relapse isolates were resistant to clarithromycin. Median time to clarithromycin resistance was 16 weeks with two drugs and 40 weeks with three drugs (P = .004). Ethambutol reduced relapses and emergence of clarithromycin resistance and should be considered an essential component of clarithromycin-based therapies for MAC bacteremia.

Adult↗
PubMed1998

Efficacy of oral ciprofloxacin vs. clarithromycin for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

In this prospective, multicenter, double-blind study, the efficacy of ciprofloxacin was compared with that of clarithromycin as therapy for patients with acute bacterial exacerbations of chronic bronchitis (ABECB) from whom a pretherapy pathogen was isolated; the efficacy was measured by the infection-free interval. Clinical and microbiological responses at the end of therapy were secondary efficacy variables. Patients randomly received either ciprofloxacin or clarithromycin (500 mg twice a day for 14 days). Three hundred seventy-six patients with acute exacerbations of chronic bronchitis were enrolled in the study of whom 234 had an ABECB. Clinical resolution was observed in 90% (89 of 99) of ciprofloxacin recipients and 82% (75 of 91) of clarithromycin recipients for whom efficacy could be evaluated. The median infection-free interval was 142 days for ciprofloxacin recipients and 51 days for clarithromycin recipients (P = .15). Bacteriologic eradication rates were 91% (86 of 95) for ciprofloxacin recipients and 77% (67 of 87) for clarithromycin recipients (P = .01). In summary, compared with clarithromycin, treatment of ABECB with ciprofloxacin was associated with a trend toward a longer infection-free interval and a statistically significantly higher bacteriologic eradication rate.

Administration, Oral↗
PubMed1999

Successful short-term suppression of clarithromycin-resistant Mycobacterium avium complex bacteremia in AIDS. California Collaborative Treatment Group.

During a randomized study of clarithromycin plus clofazimine with or without ethambutol in patients with AIDS and Mycobacterium avium complex (MAC) bacteremia, eight participants received additional antimycobacterial drugs following the detection of a clarithromycin-resistant isolate (MIC, > 8 micrograms/mL). A macrolide (seven received clarithromycin, one azithromycin) and clofazimine were continued; additional treatment included various combinations of ethambutol, ciprofloxacin, amikacin, and rifabutin. After the detection of a resistant isolate and before receipt of additional antimycobacterials, the median peak MAC colony count in blood was 105 cfu/mL (range, 8-81,500 cfu/mL). After additional antimycobacterials, the median nadir MAC colony count was 5 cfu/mL (range, 0-110 cfu/mL). Five (63%) of eight patients had a > or = 1 log10 decrease, including two who achieved negative blood cultures; all of these responses occurred in patients originally assigned to clarithromycin plus clofazimine. Treatment of clarithromycin-resistant MAC bacteremia that emerges during clarithromycin-based treatment can decrease levels of bacteremia and transiently sterilize blood cultures.

AIDS-Related Opportunistic Infections↗
PubMed1998

Clarithromycin significantly improves interleukin-12-mediated anti-Mycobacterium avium activity and abolishes toxicity in mice.

Treatment of experimental murine Mycobacterium avium (MAC) infection with interleukin-12 (IL-12) significantly decreased MAC organisms in tissue but resulted in toxicity. Because IL-12-related toxicity was seen only in infected mice, IL-12 was combined with clarithromycin in an attempt to decrease bacterial burden. Clarithromycin (200 mg/kg/day) was administered alone to M. avium-infected mice for 1 week, and from week 2, IL-12 (20 microg/kg twice per week) was added to the regimen for 4 weeks. Treatment with IL-12 resulted in 60% mortality, compared with 40% mortality in untreated control mice and 20% when IL-12 was given with clarithromycin (P < .05). Clarithromycin plus IL-12 resulted in increased activity compared with either clarithromycin or IL-12 alone in reducing the number of bacteria in spleen and blood. Although potentially toxic, IL-12 is an effective immunotherapy for MAC infection, and combination with clarithromycin reduces IL-12 toxicity.

Animals↗